The purpose of the proposed program is to promote sustainable improvements in health related basic research at the University of Kansas. The overall research topic is "Redox regulation of bio-responses in health and disease," a topic with broad implications in both normal and pathological processes. It is an important component of the on-going research of the four junior scientists in this proposal. The program design includes: 1) direct support for each pilot project, 2) activities that will enhance their progress (mentors, consultations, visiting scientists, work sessions and group interactions), 3) a molecular biology CORE facility, 4) an external advisory committee, 5) evaluation procedures to measure progress, 6) amplification features to sustain and promote further improvements, and 7) a "graduation/renewal' policy for graduating scientists out the program and bringing in new participants. The overall scientific theme includes the timely hypothesis that oxygen free radicals or nitrogen intermediates are involved in neurodegenerative diseases, diabetes, ischemia-reperfusion damage and aging, but extends the topic to the generality of redox states regulating molecular complexes. The pilot projects are: 1) Induction of "acute phase response" by redox cycling compounds; 2) Mechanism of oxidative post-translational protein modification; 3) Redox states in dopamine receptor affinity; 4) Effect of nitric oxide on redox mechanisms that control gene expression and cellular differentiation of human newborn vs. adult monocytes. The central administration enthusiastically supports the plan, the junior investigators, and considers the research appropriate for this University and compatible with the Strategic Research Plan for the 1990's. This two year program will serve as a model for promoting research on other important biomedical problems at this Institution and in collaboration with other institutions. In the final analysis, excellent research yields competitiveness, and this comes down to the right people in the right place. The Kansas IDeA strategy is: 1) mentoring, 2) CORE facilities, 3) "idea generating" work sessions with international experts, and 4) multidisciplinary, cooperative interactions. The first phase focuses on four pilot projects on redox mechanisms in biological regulation and will serve as a model for other thematic programs.